Department of biochemistry and Molecular biology
Lee Chao, PhD
Biochemistry and Molecular Biology
1971-1974 Postdoctoral Research, University of Connecticut
1970 Ph.D., Iowa State University
My laboratory's current research effort focuses on four areas. The first is to analyze the structure, organization and regulation of the genes involved in the kallikrein-kinin system. The primary function of kallikrein is to cleave low molecular weight kininogen to produce the vasoactive kinin peptide. We are analyzing the promoter of kallikrein genes by gel retardation assays and foot-printing analysis and probing the function of the kallikrein-kinin system by transgenic analysis and by homologous recombination. A number of transgenic mouse lines expressing the human tissue kallikrein gene have been generated for functional studies. Second, we are using genetically hypertensive animal models to explore the role of the kallikrein-kinin system in hypertension and to clone the defective kallikrein gene from the hypertensive animal to study the genetic defects at the molecular level. Hypertensive human populations and selected pedigrees are used to evaluate kallikrein-kinin genotypes as potential risk factors in essential hypertension and to use genotyping as a tool to identify individuals who may be predisposed to the risk factors for intervention and treatment. Third, we are developing gene delivery techniques as a tool for studying gene expression in vivo. We have successfully delivered various constructs into rat muscle, kidney, heart, lung, brain and vasculature for direct biochemical, molecular biological and physiological studies. Further development of the delivery technology could make it widely applicable for studying gene function, regulation and interaction at molecular, cellular and organismal levels. Four, we are exploring somatic gene therapy for cardiovascular and hypertensive diseases. A major objective is to improve the vector system for long-term expression in vivo. In addition, we are exploring the potential of using gene delivery to prevent tissue damage such as kidney damage caused by high salt diet and damage to the heart caused by ischemia and reperfusion.
Guo YM, Li PF, Gao L, Zhang JM, Yang ZR, Bledsoe G, Chang E, Chao L, Chao J. (2017) Kallistatin reduces vascular senescence and aging by regulating microRNA-34a-SIRT1 pathway. Aging Cell 16:837-846.
Chao J, Li PF, Chao L. (2017) Kallistatin suppresses cancer development via multi-factorial actions. Critical Reviews in Oncology/Hematology 113:71-78.
Chao J, Bledsoe G, Chao L. (2016) Kallistatin: A protective agent for vascular and organ injury. Hypertension 68:533-541.
Li P, Guo Y, Bledsoe G, Yang ZR, Chao L, Chao J. (2016) Kallistatin induces breast cancer cell apoptosis and autophagy by modulating Wnt signaling and microRNA synthesis. Experimental Cell Research 340(2):305-314.
Li P, Guo Y, Bledsoe G, Yang ZR, Fan H, Chao L, Chao J. (2015) Kallistatin treatment attenuates lethality and organ injury in mouse models of established sepsis. Critical Care 19(1):200.
Gou Y, Li P, Bledsoe G, Yang ZR, Chao L, Chao J. (2015) Kallistatin inhibits TGF-β-induced endothelial-mesenchymal transition by differential regulation of microRNA-21 and eNOS expression. Experimental Cell Research 337:103-110.
Chao J, Bledsoe G, Chao L. (2015) Kallistatin: a novel biomarker for organ injury and cancer. Invited review article for Austin Biomarkers & Diagnosis.
Lin, WC, Chen CW, Chao L, Chao J, Lin YS, Lin CF. (2015) Kallistatin protects against sepsis-related acute lung injury via inhibiting inflammation and apoptosis. Scientific Reports 5:12463.
Li PF, Bledsoe G, Yang ZR, Fan HF, Chao L, Chao J. (2014) Human kallistatin administration reduces organ injury and improves survival in a mouse model of polymicrobial sepsis. Immunology 142(2):216-226.
Chao J, Bledsoe G, Chao L. (2014) Tissue kallikrein-kinin therapy in hypertension and organ damage. Prog Drug Res 69:37-57.
Gao L, Li PF, Hagiwara M, Shen B, Bledsoe G, Chang E, Chao L, Chao J. (2014) Novel role of kallistatin in vascular repair by promoting mobility, viability, and function of endothelial progenitor cells. Journal of American Heart Association 3(5):e001194.
Chao J, Bledsoe G, Chao L. (2014) Kallikrein-kinin in stem cell therapy. Special issue of World Journal Stem Cells 6(4):448-457.
Gao L, Hang Y, Bledsoe G, Shen B, Chao L, Chao J. (2013) Tissue kallikrein-modified mesenchymal stem cells protect against ischemic cardiac injury after myocardial infarction. Circulation Journal 77:2134-2144.
Zhang J, Yang ZR, Li PF, Bledsoe G, Chao L, Chao, J. (2013) Kallistatin blocks Wnt/β-catenin signaling and cancer cell motility by binding to LRP6. Molecular and Cellular Biochemistry 379:295-301.
Lu SL, Tsai CY, Luo YH, Kuo CF, Lin WC, Chang YT, Wu JJ, Chuang WJ, Liu CC, Chao L, Chao J, Lin YS. (2013) Kallistatin modulates immune cells and confers anti-inflammatory response to protect mice from group A Streptococcal infection. Antimicrobial Agents and Chemotherapy 57:5366-5372.
Yao YY, Sheng CF, Li Y, Cong F, Ma G., Liu N, Chao J, Chao L. (2013) Tissue kallikrein-modified human endothelial progenitor cell implantation improves cardiac function via enhanced activation of Akt and increased angiogenesis. Laboratory Investigation 93:577-591.
Guo DH, Parikh S, Chao J, Pollock N, Wang X, Snieder H, Navis G, Wilson J, Bhagatwala J, Zhu H, Dong YB. (2013) Urinary prostasin excretion is associated with adiposity in non-hypertensive African American adolescents. Pediatric Research 74:206-210.
Yao YY, Li Y, Sheng Z, Yan F, Ma G, Liu N, Chao J, Chao L. (2012) Tissue kallikrein promotes cardiac neovascularization by enhancing endothelial progenitor cell migration and functional capacity. Human Gene Therapy 23(8):859-870. PMID: 22435954
Liu YY, Bledsoe G, Hagiwara M, Shen B, Chao L, Chao J. (2012) Depletion of endogenous kallistatin exacerbates renal and cardiovascular oxidative stress, inflammation and organ remodeling. Am J Physiology 303(8):F1230-1238.